Synthesis of functional heterocycles via tandem reaction

Abstract

Tandem reactions for efficient construction of nitrogen-containing heterocycles were developed. One-pot platinum (II) -catalyzed synthesis of indoles and isoquinolines has been achieved via isocyanates, which were derived from a Hof-mann-type rearrangement of 2-alkynylbenzamides and 2-alkynylbenzylamides using a hypervalent iodine reagent. As an extension of this approach, trans-2,3-dihydro-4-quinolones were synthesized via acid-catalyzed intermolecular [2+2]-cycloaddition of aldehydes and carbamates, which were formed from nucleophilic addition of alcohols to isocyanate intermediates. Direct, efficient syntheses of the benzimidazo[2,1-a]isoquinoline ring system have been achieved with 2-bromoarylaldehydes, terminal alkynes, and 1,2-phenylenediamines by a microwave-accelerated tandem process in which a Sonogashira coupling, 5-endo cyclization, oxidative aromatization, and 6-endo cyclization can be performed in a single synthetic operation. © 2013 The Pharmaceutical Society of Japan.